Document Detail

Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency.
MedLine Citation:
PMID:  2896355     Owner:  NLM     Status:  MEDLINE    
X chromosome-linked severe combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated numbers of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, we analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosomes, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. In contrast, the pattern of X chromosome inactivation in the surface IgM negative B cells, which had undergone further replication and differentiation, was significantly nonrandom in all three experiments [logarithm of odds (lod) score greater than 3.0]. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation.
M E Conley; A Lavoie; C Briggs; P Brown; C Guerra; J M Puck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  85     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1988 May 
Date Detail:
Created Date:  1988-06-09     Completed Date:  1988-06-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3090-4     Citation Subset:  IM; X    
Department of Pediatrics, Children's Hospital of Philadelphia, PA.
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MeSH Terms
B-Lymphocytes / analysis*
Cell Differentiation
Dosage Compensation, Genetic*
Heterozygote Detection*
Hybrid Cells / analysis
Immunologic Deficiency Syndromes / genetics*
Polymorphism, Restriction Fragment Length
Grant Support
A1-21477//PHS HHS; A1-25129//PHS HHS; HD-00657/HD/NICHD NIH HHS

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